title: Sustained autophagy contributes to measles virus infectivity.
abstract: The interplay between autophagy and intracellular pathogens is intricate as autophagy is an essential cellular response to fight against infections, whereas numerous microbes have developed strategies to escape this process or even exploit it to their own benefit. The fine tuned timing and/or selective molecular pathways involved in the induction of autophagy upon infections could be the cornerstone allowing cells to either control intracellular pathogens, or be invaded by them. We report here that measles virus infection induces successive autophagy signallings in permissive cells, via distinct and uncoupled molecular pathways. Immediately upon infection, attenuated measles virus induces a first transient wave of autophagy, via a pathway involving its cellular receptor CD46 and the scaffold protein GOPC. Soon after infection, a new autophagy signalling is initiated which requires viral replication and the expression of the non-structural measles virus protein C. Strikingly, this second autophagy signalling can be sustained overtime within infected cells, independently of the expression of C, but via a third autophagy input resulting from cell-cell fusion and the formation of syncytia. Whereas this sustained autophagy signalling leads to the autophagy degradation of cellular contents, viral proteins escape from degradation. Furthermore, this autophagy flux is ultimately exploited by measles virus to limit the death of infected cells and to improve viral particle formation. Whereas CD150 dependent virulent strains of measles virus are unable to induce the early CD46/GOPC dependent autophagy wave, they induce and exploit the late and sustained autophagy. Overall, our work describes distinct molecular pathways for an induction of self-beneficial sustained autophagy by measles virus.
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France ; Inserm, U1111, Lyon, France ; Ecole Normale Supérieure de Lyon, Lyon, France ; Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France ; CNRS, UMR5308, Lyon, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Richetta
authors.forename: Isabel P
authors.initials: IP
authors.lastname: Grégoire
authors.forename: Pauline
authors.initials: P
authors.lastname: Verlhac
authors.forename: Olga
authors.initials: O
authors.lastname: Azocar
authors.forename: Joël
authors.initials: J
authors.lastname: Baguet
authors.forename: Monique
authors.initials: M
authors.lastname: Flacher
authors.forename: Frédéric
authors.initials: F
authors.lastname: Tangy
authors.forename: Chantal
authors.initials: C
authors.lastname: Rabourdin-Combe
authors.forename: Mathias
authors.initials: M
authors.lastname: Faure
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000077614:Golgi Matrix Proteins; D006367:HeLa Cells; D006801:Humans; D008457:Measles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008459:Measles virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C497857:CD46 protein, human; D002352:Carrier Proteins; C434484:GOPC protein, human; D000077614:Golgi Matrix Proteins; D051916:Membrane Cofactor Protein; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1